Citalopram having the formula [A]is useful as an antidepressant. As a production method of citalopram, there is known a method comprising the use of a 5-phthalancarbonitrile compound of the formula [VI]hereinafter to be also referred to as compound [VI]. For example, compound [VI] is reacted with 3-(dimethylamino)propyl halide in the presence of a condensing agent (JP-B-61-35986). In this publication, sodium hydride is used as a condensing agent. According to this method, citalopram is obtained at a low yield, and therefore, this method is not necessarily a preferable one. Moreover, this publication does not teach how to increase the yield, not to mention the use of a different additive besides the condensing agent to improve the yield.
As a different production method of citalopram, there is reported reaction of compound [VI] with 3-(dimethylamino)propyl halide under basic conditions (WO98/19511). In this publication, lithium diisopropylamide obtained from n-butyllithium and diisopropylamine is used as a base. While the yield is improved, expensive n-butyllithium is necessary and a reaction at a very low temperature (Example, from −50° C. to −40° C.) is required, which makes the method industrially unpreferable. This publication does not teach an economical base that permits reaction in a typical temperature range, or industrial and economical production of citalopram at a high yield under basic conditions wherein specific bases are combined.
It is therefore an object of the present invention to provide an economical and industrially advantageous production method of citalopram, which affords production of citalopram at high yields.
Another object of the present invention is to provide a novel production method of a compound represented by the formula [III] to be mentioned later.